Exopolysaccharide from Bacillus subtilis Induces Anti-Inflammatory M2 Macrophages That Prevent T Cell-Mediated Disease

Abstract

Commensal bacteria contribute to immune homeostasis in the gastrointestinal tract; however, the underlying mechanisms for this are not well understood. A single dose of exopolysaccharide (EPS) from the probiotic spore-forming bacterium Bacillus subtilis protects mice from acute colitis induced by the enteric pathogen Citrobacter rodentium Adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice confers protection from disease to recipient mice. In vivo, EPS induces development of anti-inflammatory M2 macrophages in a TLR4-dependent manner, and these cells inhibit T cell activation in vitro and in C. rodentium-infected mice. In vitro, M2 macrophages inhibit CD4⁺ and CD8⁺ T cells. The inhibition of CD4⁺ T cells is dependent on TGF-β, whereas inhibition of CD8⁺ T cells is dependent on TGF-β and PD-L1. We suggest that administration of B. subtilis EPS can be used to broadly inhibit T cell activation and, thus, control T cell-mediated immune responses in numerous inflammatory diseases.